Reversibility of endothelial dysfunction in diabetes: role of polyphenols

• Published in: British journal of nutrition Vol. 116; no. 2; pp. 223 - 246
• Main Authors: Suganya, N., Bhakkiyalakshmi, E., Sarada, D. V. L., Ramkumar, K. M.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 28.07.2016
• Subjects: Angiogenesis; Animals; Anticoagulants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Blood platelets; Blood vessels; Cardiovascular Diseases - blood; Cardiovascular Diseases - physiopathology; Cardiovascular Diseases - prevention & control; Cell adhesion & migration; Cell growth; Diabetes; Diabetes Complications - blood; Diabetes Complications - physiopathology; Diabetes Complications - prevention & control; Diabetes Mellitus - blood; Diabetes Mellitus - drug therapy; Diabetes Mellitus - physiopathology; Endoplasmic Reticulum Stress; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Fibroblasts; Glucose; Homeostasis; Humans; Inflammation; Inflammation - etiology; Kinases; Leukocytes; Metabolism; Metabolism and Metabolic Studies; Nitric oxide; Nitric Oxide Synthase - blood; Oxidative Stress; Permeability; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Polyphenols - pharmacology; Polyphenols - therapeutic use; Thrombosis; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Cell signalling; Polyphenols; Endothelial dysfunction; Diabetes; XO xanthine oxidase; VEGF vascular endothelial growth factor; UPR unfolded protein responses; MCP-1 monocyte chemoattractant protein-1; IRS-1 insulin receptor substrate 1; AGE advanced glycation end products; NO∙ nitric oxide; ET-1 endothelin-1; T1D type 1 diabetes; ADMA asymmetric dimethylarginine; NOX NADPH oxidase; VCAM vascular cell adhesion molecule; cGMP cyclic GMP; eNOS endothelial nitric oxide synthase; ICAM intracellular adhesion molecule; STZ streptozotocin; AMPK AMP-activated protein kinase; SGLT2 sodium–glucose co-transporter 2; GLP-1 glucagon-like peptide-1; ER endoplasmic reticulum; BH4 (6R)-5; IRE1 inositol-requiring enzyme 1; ROS reactive oxygen species; 8-tetrahydro-L-biopterin; Nrf2 nuclear factor-E2-related factor 2; 6; 7; EGCG epigallocatechin gallate; T2D type 2 diabetes; PKC protein kinase C
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114516001884

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.